Drug & supplement interaction

Indian Long Pepper + Drospirenone, Estetrol

Drospirenone, Estetrol brand name: Nextstellis.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Drospirenone, Estetrol falls into 2 drug categories that Indian Long Pepper can interact with; the most serious is rated moderate. Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Indian Long Pepper and Drospirenone, Estetrol

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Indian Long Pepper interacts with whole categories of medication. Drospirenone, Estetrol falls into 2 of those categories, so it can interact with Indian Long Pepper in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Drospirenone, Estetrol

Drospirenone, Estetrol falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Indian Long Pepper interacts with.

Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP3A4.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Your birth control pill, Nextstellis, contains drospirenone and estetrol, two hormones that your liver partly clears using an enzyme called CYP3A4. Piperine, the active compound in Indian long pepper, may slow that enzyme down a bit. In theory, this could let those hormone levels drift a little higher, which might mean more of the usual side effects like breast tenderness, nausea, bloating, headaches, or mood changes.

I want to be honest about how soft this evidence is. It comes only from lab (test tube) studies, not from real people, so we truly don't know if it matters in everyday life. A sprinkle of pepper on food is very unlikely to do anything. If you take concentrated long pepper supplements regularly, just mention it to your pharmacist or doctor so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 2

Drospirenone, Estetrol also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, Indian long pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, can inhibit P-glycoprotein.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with your birth control pill (Nextstellis, which combines drospirenone and estetrol). One of the active compounds in Indian long pepper, called piperine, may block a transporter in your gut and body known as P-glycoprotein. In a test-tube setting, that blocking action could let a bit more of certain medicines get absorbed, which theoretically might nudge your hormone levels slightly higher.

Now, I want to be honest about how soft this evidence is. This is based on lab research, not real people taking the two together, so the actual risk is uncertain. If it did matter, you might notice more typical pill side effects like nausea, breast tenderness, or spotting. A sprinkle of pepper in food is very unlikely to do anything. If you take concentrated pippali supplements regularly, just give your pharmacist or doctor a heads up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  2. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Indian Long Pepper Also Interacts With Other Medications

Indian Long Pepper has 892 moderate, 3 minor known drug interactions in our database — the Drospirenone, Estetrol one above is among them. If you take anything else, check it against the full list below.

Moderate 892 Minor 3 No known interaction 1,935 (incl. Drospirenone, Estetrol)
Taking anything else?

Check Another of Your Medications Against Indian Long Pepper

Covers the 2,830 medications we’ve checked against Indian Long Pepper. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Drospirenone, Estetrol

This page covers Indian Long Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Drospirenone, Estetrol page lists 245 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 200 moderate · 39 minor.

From our pharmacist’s overview on the Drospirenone, Estetrol page

“The stakes with Nextstellis (drospirenone and estetrol) are the ones that come with any birth control pill, because an interaction that lowers its hormone levels can mean an unplanned pregnancy, and I would treat this list with genuine seriousness. Most of what is here changes how the body handles the hormones.”

Reviewed by 2 · Jul 18, 2026

Open the Drospirenone, Estetrol interaction page

One more smart check

Taking Indian Long Pepper as Part of a Dietary Supplement Product? Check It for Interactions

We hold 597 real supplement products containing Indian Long Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Long Pepper. Your product may carry other ingredients that interact with Drospirenone, Estetrol too, on top of Indian Long Pepper — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Indian Long Pepper and Drospirenone, Estetrol Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Indian Long Pepper
Top 25%

#202 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Drospirenone, Estetrol
Top half

#1,086 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Indian Long Pepper

What is Indian Long Pepper?

Indian Long Pepper
  • Digestive upset
  • Respiratory and cough complaints
  • Boosting absorption of other supplements
  • Pain and inflammation
  • General wellness in Ayurveda

Indian long pepper (pippali) is a spice long used in Ayurvedic medicine and is best known for its piperine content, which may increase how well the body absorbs certain other substances. Modern human research on its health benefits is limited, so use it cautiously and let your pharmacist or doctor know if you take it regularly.

Read the full Indian Long Pepper monograph & all interactions
Keep checking

Other Drugs & Indian Long Pepper

Browse every other medication we’ve checked against Indian Long Pepper — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
892Moderate
3Minor
1,934No known interaction
892 Moderate 3 Minor 1,934 No interaction
Moderate

892 interactions

Showing 60 of 892 moderate interactions — see all 892 on the Indian Long Pepper page.

Minor

3 interactions

No interaction 1,934 drugs checked — show the list

We also checked Indian Long Pepper against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,934 medications checked with no known interaction — see the full Indian Long Pepper list.

See the full Indian Long Pepper interactions page
See every supplement checked against Drospirenone, Estetrol, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Indian Long Pepper monograph › Uses, safety, and every drug interaction in one place Drospirenone, Estetrol supplement interactions › Every supplement checked against Drospirenone, Estetrol, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Indian Long Pepper and Drospirenone, Estetrol Together: Common Questions

Can you take Indian Long Pepper with Drospirenone, Estetrol?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Indian Long Pepper and Drospirenone, Estetrol?
Drospirenone, Estetrol belongs to more than one drug category, and Indian Long Pepper interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Indian Long Pepper and Drospirenone, Estetrol interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.